The goal of the proposed research is to achieve a thorough understanding of the mechanism by which Delta, a Drosophila neurogenic gene, affects cell fate specification, division, and differentiation during embryonic and postembryonic development. D1 encodes a cell surface protein, the extracellular domain of which includes multiple repeats of a protein- protein interaction motif related to vertebrate epidermal growth factor. functional analyses imply that the protein encoded by D1 (Delta) can interact with the protein product of the Notch (N) gene (Notch) as a signal that is required for intercellular communication processes essential for the specification of cell fates. We will employ somatic mosaic analysis in a number of imaginal tissues to determine whether Delta functions in a cell-nonautonomous fashion (i.e., as a potential signal) or a cell-autonomous fashion (i.e., as a potential receptor). We will employ a combination of molecular biological, cell biological, immunohistochemical, and genetic tools to analyze the trafficking of Delta within expressing cells and to determine whether Delta, or a portion thereof, is transferred between cells in vivo. We will employ genetic modifier screens to identify genes that encode products with which Delta may interact in vivo. Our investigations of the mechanism of Delta protein function in vivo are intended to advance our understanding of mechanisms of intermolecular and intercellular interaction that underlie a variety of developmental processes in higher eukaryotes. Given that Delta function affects the development of neural and epidermal stem cell populations, the results of these studies may prove useful in the development of cell replacement therapies for the restoration of neural and epidermal tissues lost as a result of disease or injury. Given that homologues of a protein with which Delta interacts (Notch) are also found in vertebrates, these studies may contribute directly to our understanding of the functions of homologues of Drosophila neurogenic genes in vertebrates.